Compositions useful for the treatment of gastrointestinal disorders

1. A composition comprising a guanylate cyclase receptor agonist (GCRA) peptide consisting essentially of the sequence of any one of 1-44, 56-90, 99-107, 109-173, 175-207, 209-249, 251-291, 302-311, 313-346, 371, and 372 and 5-aminosalicyclic acid (5-ASA) or a derivative or a pharmaceutically acceptable salt thereof, wherein said 5-ASA or derivative or pharmaceutically acceptable salt thereof is covalently linked to the N terminus and/or the C terminus of said peptide, wherein said composition comprises a glycosidic bond between the peptide and sugar residues of the 5-ASA molecule, and wherein when said glycosidic bond is cleaved, the peptide and 5-ASA molecule are released to produce a colon-specific effect.

2. The composition of claim 1 , wherein said 5-ASA or derivative or pharmaceutically acceptable salt thereof is covalently linked to the N terminus and/or the C terminus of said peptide.

3. The composition of claim 2 , wherein said peptide is selected from the group consisting of

[5-ASA]-GCRA (formula A),

GCRA-[5-ASA] (formula B),

and

[5-ASA]-GCRA-[5-ASA] (formula C).

4. The composition of claim 1 , further comprising a pharmaceutical carrier, excipient or diluent.

5. The composition of claim 1 , wherein said derivative is sulfasalazine.

6. The composition of claim 1 , wherein said peptide is a bicyclic peptide comprising the sequence of any one of SEQ ID NOs: 1-54, 99-207, 250-346, 371, and 372.

7. The composition of claim 1 further comprising an enteric coating comprising a methacrylic acid copolymer.

8. The composition of claim 7 , wherein the methacrylic acid copolymer is selected from among the EUDRAGIT polymers.

9. A method for treating a condition that responds to enhanced cGMP levels in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a composition of claim 1 , wherein said composition is administered in an amount sufficient to increase water transport in the gastrointestinal tract and induce cGMP production in a gastrointestinal epithelial cell.

10. The method of claim 9 , wherein the condition is selected from the group consisting of ulcerative colitis, Crohn's disease, irritable bowel syndrome (IBS), non-ulcer dyspepsia, chronic intestinal pseudo-obstruction, functional dyspepsia, colonic pseudo-obstruction, duodenogastric reflux, constipation, constipation associated with use of opiate pain killers, post-surgical constipation, constipation associated with neuropathic disorders, gastroesophageal reflux disease (GERD), Celiac disease, gastroparesis, heartburn, poor gastrointestinal motility, hypertension, colon cancer, lipid metabolism disorders, and obesity.

11. A method of colonic cleansing, comprising administering to a subject in need thereof an effective amount of a composition of claim 2 .

12. The method of claim 9 , 10 , or 11 , further comprising administering a therapeutically effective amount of a cGMP-dependent phosphodiesterase inhibitor.

13. The method of claim 12 , wherein said cGMP-dependent phosphodiesterase inhibitor is administered either concurrently or sequentially with said peptide.

14. The method of claim 12 , wherein said cGMP-dependent phosphodiesterase inhibitor is selected from the group consisting of sulindac sulfone, zaprinast, motapizone, vardenafil, and sildenafil.

15. The method of claim 9 or 10 , further comprising administering a therapeutically effective amount of at least one anti-inflammatory agent.

16. The method of claim 15 , wherein said anti-inflammatory agent is a steroid or nonsteroid anti-inflammatory drug (NSAID).